A humanized anti-DLL4 antibody promotes dysfunctional angiogenesis and inhibits breast tumor growth

@article{Jia2016AHA,
  title={A humanized anti-DLL4 antibody promotes dysfunctional angiogenesis and inhibits breast tumor growth},
  author={Xuelian Jia and Wenyi Wang and Zhuobin Xu and Shijing Wang and Tong Wang and Min Wang and Min Wu},
  journal={Scientific Reports},
  year={2016},
  volume={6}
}
Blockage of Delta-like 4 (DLL4)-directed Notch signaling induces excessive tip cell formation and endothelial proliferation resulting in dysfunctional angiogenesis in tumors. MMGZ01, as a murine anti-human DLL4 monoclonal antibody, specifically binds to human DLL4 and blocks Notch pathway. Here, the structure of MMGZ01 variable fragment (Fv) was established and framework region (FR) residues which supported complementarily determining region (CDR) loop conformation were identified. Important… 
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Taken together, Notch signaling components are aberrantly overexpressed in colorectal tumors, and development of therapeutics targeting the Notch pathway may prove to be beneficial in the management of coloreCTal cancers.
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The Notch signaling pathway has been implicated in cell fate determination and differentiation in many tissues. Accumulating evidence points toward a pivotal role in blood vessel formation, and the
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TLDR
It is proved that the full-length antibody targeting human VEGFR2 has potential clinical applications in the treatment of cancer and other diseases where pathological angiogenesis is involved and is capable of mediating tumor cell killing in presence of effector cells.
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This review aims to provide current perspectives on the function of the Dll4-Notch signaling axis during tumor angiogenesis and as a target for anti-angiogenic cancer therapy.
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TLDR
It is shown that Numb-mediated control on Notch signaling is lost in ∼50% of human mammary carcinomas, due to specific Numb ubiquitination and proteasomal degradation.
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TLDR
It is shown that one ligand for the Notch receptors, Delta-like ligand 4 (DLL4), is normally induced by VEGF and is a negative-feedback regulator that restrains vascular sprouting and branching and results in excessive, non-productive angiogenesis.
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TLDR
D14 is high in the vasculature of xenograft human tumors in the mouse, in endogenous human tumors and is regulated by hypoxia, and possible new targets for antiangiogenic tumor therapy are suggested.
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TLDR
It is shown that increased RBP-Jkappa-dependent Notch signaling is sufficient to transform normal breast epithelial cells and that the mechanism of transformation is most likely through the suppression of apoptosis, suggesting that inhibition of notch signaling may be a therapeutic strategy for this disease.
Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis
TLDR
Evidence is presented that delta-like 4 (Dll4)–Notch1 signalling regulates the formation of appropriate numbers of tip cells to control vessel sprouting and branching in the mouse retina, and modulators of Dll4 or Notch signalling, such as γ-secretase inhibitors developed for Alzheimer's disease, might find usage as pharmacological regulators of angiogenesis.
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TLDR
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